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The 2001 foot-and-mouth disease epidemic was controlled by culling of infectious premises and pre-emptive culling intended to limit the spread of disease. animal density regions, more extensive fixed radius ring culling is optimal. Analysis of the 2001 data suggests that the lowest-risk U-104 manufacture CPs were generally prioritized for culling, however, even in this case, the policy is U-104 manufacture usually predicted to be effective. A sensitivity analysis and the development of a spatially heterogeneous policy show that the optimal culling level depends upon the basic reproductive ratio of the contamination and the width of the dispersal kernel. These analyses highlight an important and probably quite general result: optimal control is highly dependent upon the distance over which the pathogen can be transmitted, the transmission rate of contamination and local demography where the disease is launched. 2001; Klinkenberg 2003; Donnelly 2006; Savill 2006, 2008). On occasion, the culling programmes can be very extensive, involving millions of animals on thousands of farms. One well-known and much discussed example of culling to control livestock disease occurred during the UK 2001 epidemic of FMD. This was an exceptionally well-recorded epidemic, providing useful data around the spread of an infection between farms over a complex landscape. Although there have been several detailed analyses of these data (Ferguson 2001; Keeling U-104 manufacture 2001; Chis Ster 2009; Deardon in press), presently there remains some controversy over the true impact of the culling programmes launched at the time (e.g. Kitching 2007; Tildesley 2007). The UK 2001 FMD data provide an opportunity to explore the expected impact of different culling strategies, particularly the extent of pre-emptive culling and how best to target the pre-emptive culling effort (echoing previous work asking the same questions with regard to reactive vaccination programmes: Keeling 2003; Tildesley 2006). This paper has U-104 manufacture three elements. First, we present data around the culling programme implemented during the UK 2001 FMD epidemic, paying particular attention to how pre-emptive culling was targeted. Second, we use an adapted version of a stochastic spatio-temporal farm-based model (Keeling 2001) to carry out a retrospective model-based analysis of the 2001 epidemic to estimate the impact of pre-emptive culling in practice. Finally, the model is used prospectively to examine the effect of different culling strategies on controlling FMD outbreaks in general, considering both variations in the transmissibility of disease and the regions of the UK in which it is launched. 2.?The 2001 FMD epidemic During 2001, the UK experienced an epidemic of FMD that lasted seven months with disease reported on some 2026 infected premises (IPs). In addition to the 2026 IPs, 250 farms were culled as suspected FMD cases, and animals on a further 8570 premises were culled pre-emptively. These data were recorded in the disease control system TEK (DCS) database and the reasons for the pre-emptive culls can be broken down into two main groups. (a) Culls of farms at risk (5312 farms) Farms at elevated risk of harbouring disease were identified on a case-by-case basis and were culled accordingly. Such farms were officially designated as either traditional dangerous contacts (DCs) or contiguous premises (CPs). DCs were defined as premises where animals have been in direct contact with infected animals or have, in any way, become exposed to contamination and CPs as a category of dangerous contacts where animals may have been exposed to contamination on neighbouring infected premises (Anderson 2002). These two kinds of pre-emptive cull were imperfectly distinguished in practice (in theory some farms could have been culled under either heading, with such farms sometimes being recorded as a DC, sometimes as a CP and sometimes as other). CP culling was officially launched on 27 March 2001, and partly calm from 26 April 2001 by allowing the exemption of some cattle and rare breeds from culling. Local discretion in CP culling was also permitted (Honhold 2004)veterinary inspectors were U-104 manufacture given the power to cull only parts of a holding if it was felt the entire holding had not been exposed (National Audit Office 2002). In practice, CP culling was never fully implemented and not all contiguous farms experienced their livestock culled (National Audit Office 2002). (b) Three kilometre cull and local culls (3260 farms) A cull of 700 000 sheep on 2000 farms in north Cumbria and south west Scotland was approved on 15 March 2001 and formally implemented from 22 March.